Update on Early-Life T Cells: Impact on Oral Rotavirus Vaccines.

Rotavirus infection continues to be a significant public health problem in developing countries, despite the availability of several vaccines. The efficacy of oral rotavirus vaccines in young children may be affected by significant immunological differences between individuals in early life and adults. Therefore, understanding the dynamics of early-life systemic and mucosal immune responses and the factors that affect them is essential to improve the current rotavirus vaccines and develop the next generation of mucosal vaccines. This review focuses on the advances in T-cell development during early life in mice and humans, discussing how immune homeostasis and response to pathogens is established in this period compared to adults. Finally, the review explores how this knowledge of early-life T-cell immunity could be utilized to enhance current and novel rotavirus vaccines.

Impact of rotavirus vaccination on diarrheal disease burden of children in South America.

INTRODUCTION: Rotavirus is a leading cause of severe diarrheal disease and death in children under five years of age worldwide. Vaccination is one of the most important public health interventions to reduce this significant burden. AREAS COVERED: This literature review examined vaccination coverage, hospitalization rate, mortality, genotypic distribution, immunogenicity, cost-effectiveness, and risk versus benefit of rotavirus vaccination in children in South America. Nine out of twelve countries in South America currently include a rotavirus vaccine in their national immunization program with coverage rates in 2022 above 90%. EXPERT OPINION: Introduction of the rotavirus vaccination has led to a marked reduction in hospitalizations and deaths from diarrheal diseases in children under 5 years, particularly infants under 1 year, in several South American countries. In Brazil, hospitalizations decreased by 59% and deaths by 21% (30-38% in infants). In Peru, hospitalizations in infants fell by 46% and deaths by 37% (56% in infants). Overall, data suggest that rotavirus vaccination has reduced rotavirus deaths by 15-50% in various South American countries. There is some evidence that immunity wanes after the age of 1-year old. Ongoing surveillance of vaccine coverage and changes in morbidity and mortality is important to maximize protection against this disease.

Immunogenicity of RV1 and RV5 vaccines administered in standard and interchangeable mixed schedules: a randomized, double-blind, non-inferiority clinical trial in Mexican infants.

Introduction: Rotavirus-associated diarrheal diseases significantly burden healthcare systems, particularly affecting infants under five years. Both Rotarix™ (RV1) and RotaTeq™ (RV5) vaccines have been effective but have distinct application schedules and limited interchangeability data. This study aims to provide evidence on the immunogenicity, reactogenicity, and safety of mixed RV1-RV5 schedules compared to their standard counterparts. Methods: This randomized, double-blind study evaluated the non-inferiority in terms of immunogenicity of mixed rotavirus vaccine schedules compared to standard RV1 and RV5 schedules in a cohort of 1,498 healthy infants aged 6 to 10 weeks. Participants were randomly assigned to one of seven groups receiving various combinations of RV1, and RV5. Standard RV1 and RV5 schedules served as controls of immunogenicity, reactogenicity, and safety analysis. IgA antibody levels were measured from blood samples collected before the first dose and one month after the third dose. Non-inferiority was concluded if the reduction in seroresponse rate in the mixed schemes, compared to the standard highest responding scheme, did not exceed the non-inferiority margin of -0.10. Reactogenicity traits and adverse events were monitored for 30 days after each vaccination and analyzed on the entire cohort. Results: Out of the initial cohort, 1,365 infants completed the study. Immunogenicity analysis included 1,014 infants, considering IgA antibody titers ≥20 U/mL as seropositive. Mixed vaccine schedules demonstrated non-inferiority to standard schedules, with no significant differences in immunogenic response. Safety profiles were comparable across all groups, with no increased incidence of serious adverse events or intussusception. Conclusion: The study confirms that mixed rotavirus vaccine schedules are non-inferior to standard RV1 and RV5 regimens in terms of immunogenicity and safety. This finding supports the flexibility of rotavirus vaccination strategies, particularly in contexts of vaccine shortage or logistic constraints. These results contribute to the global effort to optimize rotavirus vaccination programs for broader and more effective pediatric coverage.Clinical trial registration: ClinicalTrials.gov, NCT02193061.

Etiologies of Mild and Moderate Diarrheal Illness among Children in Consuelo, Dominican Republic.

Since the rotavirus vaccine was included in the Dominican Republic's national immunization schedule in 2012, the microbiologic etiologies of acute gastroenteritis have not been described. This study aimed to determine the contribution of rotavirus as an etiology of acute gastroenteritis over a 12-month period in children under 5 years of age in both an inpatient and an outpatient setting in Consuelo, Dominican Republic. All children who were seen at Niños Primeros en Salud clinic or admitted to Hospital Municipal Dr. Angel Ponce Pinedo for acute gastroenteritis during January 2021-April 2022 were enrolled in the study. Stools were evaluated for rotavirus, enteric parasites, and pathogenic bacteria. Pathogen detection was compared between outpatients and inpatients and on the basis of child's vaccination status. From 181 children enrolled, 170 stool samples were collected, 28 (16.5%) from inpatients and 142 (83.5%) from outpatients. Rotavirus was the most commonly detected pathogen and was proportionately more common among hospitalized children, with nine (32.1%) cases among hospitalized children and 16 (11.3%) among outpatient children. (Pearson χ2 = 8.1, P = 0.004). Among patients with a positive rotavirus result, vaccination rate was lower among moderate (hospitalized) (three of six; 50%) compared with mild (outpatient) diarrhea patients (12 of 15; 80%). Giardia lamblia (10%) was the next most prevalent pathogen detected in both inpatients and outpatients using standard laboratory measures. Despite the availability of rotavirus vaccination, rotavirus remains a common cause of gastrointestinal illness among children under 5 years of age in our cohort. Incomplete vaccination status was associated with hospitalization for gastrointestinal illness.

Nonsecretor Phenotype Is Associated With Less Risk of Rotavirus-Associated Acute Gastroenteritis in a Vaccinated Nicaraguan Birth Cohort.

BACKGROUND: Histo-blood group antigens (HBGAs) have been associated with rotavirus vaccine take; but the effect of these HBGAs on rotavirus incidence and risk remains poorly explored in vaccinated populations. METHODS: Rotavirus-associated acute gastroenteritis (AGE) was assessed in 444 Nicaraguan children followed from birth until 3 years of age. AGE episodes were tested for rotavirus by reverse-transcription quantitative polymerase chain reaction, and saliva or blood was used to determine HBGA phenotypes. Cox proportional hazards models were used to estimate the relative hazard of rotavirus AGE by HBGA phenotypes. RESULTS: Rotavirus was detected in 109 (7%) stool samples from 1689 AGE episodes over 36 months of observation between June 2017 and July 2021. Forty-six samples were successfully genotyped. Of these, 15 (35%) were rotavirus vaccine strain G1P[8], followed by G8P[8] or G8P[nt] (11 [24%]) and equine-like G3P[8] (11 [24%]). The overall incidence of rotavirus-associated AGE was 9.2 per 100 child-years, and was significantly higher in secretor than nonsecretor children (9.8 vs 3.5/100 child-years, P = .002). CONCLUSIONS: The nonsecretor phenotype was associated with decreased risk of clinical rotavirus vaccine failure in a vaccinated Nicaraguan birth cohort. These results show the importance of secretor status on rotavirus risk, even in vaccinated children.

Cost-effectiveness analysis measuring the total costs against the health benefits of three different rotavirus vaccines for Mexico.

Rotavirus (RV) infection causes acute rotavirus gastroenteritis (RVGE) in infants. Safe and effective RV vaccines are available, of which Mexico has included one in its national immunization program (NIP) since 2007. Health outcome gains, expressed in quality-adjusted life years (QALYs), and cost improvements are important additional factors for the selection of a NIP vaccine. These two factors were analyzed here for Mexico over one year implementing three RV vaccines: 2-dose Rotarix (HRV), versus 3-dose RotaTeq (HBRV), and 3-dose Rotasiil (BRV-PV), presented in a 1-dose or 2-dose vial). HRV would annually result in discounted QALY gains of 263 extra years compared with the other vaccines by averting an extra 24,022 homecare cases, 10,779 medical visits, 392 hospitalizations, and 12 deaths. From a payer's perspective and compared with HRV, BRV-PV 2-dose vial and BRV-PV 1-dose vial would annually result in $13,548,179 and $4,633,957 net savings, respectively, while HBRV would result in $3,403,309 extra costs. The societal perspective may also show savings compared with HRV for BRV-PV 2-dose vial of $4,875,860, while BRV-PV 1-dose vial and HBRV may show extra costs of $4,038,363 and $12,075,629 respectively. HRV and HBRV were both approved in Mexico, with HRV requiring less investment than HBRV with higher QALY gains and cost savings. The HRV vaccine produced those higher health gains due to its earlier protection and greater coverage achieved after its schedule completion with two doses only, providing full protection at four months of age instead of longer periods for the other vaccines.

Rotavirus (RV) infection causes acute diarrhea in infants and can be life-threatening. Several safe and effective vaccines against RV and its complications exist. For many governments choosing vaccines for national immunization programs, total costs or savings and health gains are important factors in the selection process. We compared the costs and health benefits of three RV vaccines for Mexico: HRV, HBRV, and BRV-PV, that have different dosing schedules: two doses for HRV and three doses for HBRV and BRV-PV. HRV is currently part of the national immunization program in Mexico. HRV would result in more health benefits as it incurs fewer RV-related cases, medical visits, hospitalizations, and infant deaths than the other vaccines due to its early protection achieved after only two doses to complete its schedule. However, from a payer's perspective, the least expensive vaccine was BRV-PV, while HRV was less expensive than HBRV. From a societal perspective, also accounting for families' costs and loss in income due to an infant's RV disease, and the families' costs and loss in income when accompanying the infant to the vaccination center, the HRV vaccine was less expensive than HBRV and BRV-PV presented in a 1-dose vial, while more expensive than BRV-PV presented in a 2-dose vial. HRV and HBRV are both approved in Mexico, although HBRV requires a greater investment at lower health benefits than HRV, from both a payer's and a societal perspective. A 2-dose vaccination scheme is an important asset for the economic value of this vaccination program.

A Comparison of Pathogen Detection and Risk Factors among Symptomatic Children with Gastroenteritis Compared with Asymptomatic Children in the Post-rotavirus Vaccine Era.

OBJECTIVE: To describe demographics, pathogen distribution/seasonality, and risk factors in children seeking care for acute gastroenteritis (AGE) at a midwestern US emergency department during 5 postrotavirus vaccine years (2011-2016), and further, to compare the same data with matched healthy controls (HC). STUDY DESIGN: AGE and HC participants <11 years old enrolled in the New Vaccine Surveillance Network study between December 2011 to June 2016 were included. AGE was defined as ≥3 diarrhea episodes or ≥1 vomiting episode. Each HC's age was similar to an AGE participant's age. Pathogens were analyzed for seasonality effects. Participant risk factors for AGE illness and pathogen detections were compared between HC and a matched subset of AGE cases. RESULTS: One or more organisms was detected in 1159 of 2503 children (46.3%) with AGE compared with 99 of 537 HC (17.3%). Norovirus was detected most frequently among AGE (n = 568 [22.7%]) and second-most frequently in HC (n = 39 [6.8%]). Rotavirus was the second most frequently detected pathogen among AGE (n = 196 [7.8%]). Children with AGE were significantly more likely to have reported a sick contact compared with HC, both outside the home (15.6% vs 1.4%; P < .001) and inside the home (18.6% vs 2.1%; P < .001). Daycare attendance was higher among children with AGE (41.4%) compared with HC (29.5%; P < .001). The Clostridium difficile detection rate was slightly higher among HC (7.0%) than AGE (5.3%). CONCLUSIONS: Norovirus was the most prevalent pathogen among children with AGE. Norovirus was detected in some HC, suggesting potential asymptomatic shedding among HC. The proportion of AGE participants with a sick contact was approximately 10 times greater than that of HC.

Effectiveness of Pentavalent Rotavirus Vaccine in Shanghai, China: A Test-Negative Design Study.

OBJECTIVE: To evaluate vaccine effectiveness (VE) of a live oral pentavalent rotavirus vaccine (RotaTeq, RV5) among young children in Shanghai, China, via a test-negative design study. STUDY DESIGN: We consecutively recruited children visiting a tertiary children's hospital for acute diarrhea from November 2021 to February 2022. Information on clinical data and rotavirus vaccination was collected. Fresh fecal samples were obtained for rotavirus detection and genotyping. To evaluate VE of RV5 against rotavirus gastroenteritis among young children, unconditional logistic regression models were conducted to compare ORs for vaccination between rotavirus-positive cases and test-negative controls. RESULTS: A total of 390 eligible children with acute diarrhea were enrolled, including 45 (11.54%) rotavirus-positive cases and 345 (88.46%) test-negative controls. After excluding 4 cases (8.89%) and 55 controls (15.94%) who had received the Lanzhou lamb rotavirus vaccine, 41 cases (12.39%) and 290 controls (87.61%) were included for the evaluation of RV5 VE. After adjustment for potential confounders, the 3-dose RV5 vaccination showed 85% (95% CI, 50%-95%) VE against mild to moderate rotavirus gastroenteritis among children aged 14 weeks to ≤4 years and 97% (95% CI, 83%-100%) VE among children aged 14 weeks to ≤2 years with genotypes G8P8, G9P8, and G2P4 represented 78.95%, 18.42%, and 2.63% of circulation strains, respectively. CONCLUSIONS: A 3-dose vaccination of RV5 is highly protective against rotavirus gastroenteritis among young children in Shanghai. The G8P8 genotype prevailled in Shanghai after RV5 introduction.

Circulation of Vaccine-derived Rotavirus G1P[8] in a Vulnerable Child Cohort in Rio de Janeiro.

BACKGROUND: The expansion of rotavirus (RV) immunization in several countries reduced the burden of acute diarrheal disease (ADD) and diarrhea-associated mortality. Although community transmission of live attenuated monovalent rotavirus vaccine (G1P[8] RV1) virus has been demonstrated in children and household contacts, fecal shedding of these strains in neonates and infants under six weeks of age has never been demonstrated. The objective of the study was to assess ADD and rotavirus vaccine strain shedding before and after immunization through 24 months of age. METHODS: This was a prospective cohort study in a low-resource community in which stool samples were collected from neonates from 15 to 45 days of age every 2 weeks, after both doses of G1P[8] RV1, and in subsequent ADD episodes until 2 years of age. RV was detected and genotyped in stool samples by RT-PCR. RESULTS: We enrolled 242 participants who were followed for an average of 23 months. The specific prevalence of G1P[8] RV1 virus was 3.3% in neonates and infants less than six weeks of age, 50% after the first dose, and 25.6% after the second dose. Among the 70 participants with ADD, G1P[8] RV1 virus was identified in only one participant (1.4% prevalence). CONCLUSIONS: In vaccinated children, there were no breakthrough infections with G1P[8] RV1 and ADD was rare supporting high vaccine effectiveness. We observed G1P[8] RV1 virus shedding among neonates and infants before the first vaccine dose, providing evidence of transmission of the vaccine strain from immunized children to those who are not yet vaccinated.

Enteropathogen Changes After Rotavirus Vaccine Scale-up.

OBJECTIVES: To inform next steps in pediatric diarrhea burden reduction by understanding the shifting enteropathogen landscape after rotavirus vaccine implementation. METHODS: We conducted a case-control study of 1788 medically attended children younger than 5 years, with and without gastroenteritis, after universal rotavirus vaccine implementation in Peru. We tested case and control stools for 5 viruses, 19 bacteria, and parasites; calculated coinfection-adjusted attributable fractions (AFs) to determine pathogen-specific burdens; and evaluated pathogen-specific gastroenteritis severity using Clark and Vesikari scales. RESULTS: Six pathogens were independently positively associated with gastroenteritis: norovirus genogroup II (GII) (AF 29.1, 95% confidence interval [CI]: 28.0-32.3), rotavirus (AF 8.9, 95% CI: 6.8-9.7), sapovirus (AF 6.3, 95% CI: 4.3-7.4), astrovirus (AF 2.8, 95% CI: 0.0-4.0); enterotoxigenic Escherichia coli heat stable and/or heat labile and heat stable (AF 2.4, 95% CI: 0.6-3.1), and Shigella spp. (AF 2.0, 95% CI: 0.4-2.2). Among typeable rotavirus cases, we most frequently identified partially heterotypic strain G12P[8] (54 of 81, 67%). Mean severity was significantly higher for norovirus GII-positive cases relative to norovirus GII-negative cases (Vesikari [12.7 vs 11.8; P < .001] and Clark [11.7 vs 11.4; P = .016]), and cases in the 6- to 12-month age range relative to cases in other age groups (Vesikari [12.7 vs 12.0; P = .0002] and Clark [12.0 vs 11.4; P = .0016]). CONCLUSIONS: Norovirus is well recognized as the leading cause of pediatric gastroenteritis in settings with universal rotavirus vaccination. However, sapovirus is often overlooked. Both norovirus and sapovirus contribute significantly to the severe pediatric disease burden in this setting. Decision-makers should consider multivalent vaccine acquisition strategies to target multiple caliciviruses in similar countries after successful rotavirus vaccine implementation.

Evaluación de distintas estrategias de vacunación frente a rotavirus en España. Seguridad, eficacia, efectividad y eficiencia / Evaluation of several vaccination strategies against rotavirus in Spain. Safety, efficacy, effectiveness and efficiency

INTRODUCCIÓN En España, desde 2006, están comercializadas 2 vacunas contra rotavirus, Rotarix® (vacuna monovalente, comercializada por GlaxoSmithKline (GSK)) y RotaTeq® (vacuna pentavalente, comercializada por Merck Sharp and Dome (MSD)). La vacunación frente a rotavirus no está incluida como vacuna universal en el calendario de vacunación a lo largo de toda la vida en España, pero sí en el de vacunación en menores y adolescentes (< 18 años) con condiciones de riesgo. En concreto está indicada a partir de las 6 semanas de vida en nacidos entre las semanas 25-27 (según vacuna utilizada) y 32 de gestación, clínicamente estables y sin contraindicaciones. OBJETIVOS Este informe se realiza a solicitud del Ministerio de Sanidad para evaluar la conveniencia de implantar distintas estrategias vacunales frente a rotavirus en España. Los objetivos del informe son: • Evaluar la seguridad, eficacia y efectividad de las vacunas frente a rotavirus en menores de un año. • Evaluar la eficiencia de la vacunación universal y de la vacunación a población de riesgo en comparación con la no vacunación. • Estimar el posible impacto presupuestario que podría tener la implantación de la vacunación universal frente a rotavirus en España. METODOLOGÍA Revisiones sistemáticas Se han llevado a cabo revisiones sistemáticas (RS) sobre seguridad, eficacia, efectividad y eficiencia. Se han seleccionado a

INTRODUCTION Two rotavirus vaccines, Rotarix® (monovalent vaccine, marketed by GlaxoSmithKline (GSK)) and RotaTeq® (pentavalent vaccine, marketed by Merck Sharp and Dome (MSD)), have been marketed in Spain since 2006. Rotavirus vaccination is not included as a universal vaccine in the lifelong vaccination schedule in Spain, but it is included in the vaccination schedule for children and adolescents (< 18 years) at risk. Specifically, it is indicated from 6 weeks of life in children born between 25-27 weeks (depending on the vaccine used) and 32 weeks of gestation, clinically stable and without contraindications. OBJECTIVES This report is carried out at the request of the Ministry of Health to evaluate the appropriateness of implementing different rotavirus vaccination strategies in Spain. The objectives of the report are: • To evaluate the safety, efficacy and effectiveness of rotavirus vaccines in children under one year of age. • To assess the efficiency of universal vaccination and vaccination of at-risk populations compared to non-vaccination. • To estimate the possible budgetary impact of the implementation of universal vaccination against rotavirus in Spain. METHODOLOGY Systematic reviews Systematic reviews (SR) on safety, efficacy, effectiveness and efficiency were

Impact of Monovalent Rotavirus Vaccine on Rotavirus Hospitalizations among Children Younger Than 5 Years of Age in the Ouest and Artibonite Departments, Haiti, 2013 to 2019.

Rotavirus is responsible for 26% of diarrheal deaths in Latin America and the Caribbean. Haiti introduced the monovalent rotavirus vaccine in April 2014. The objective of this analysis is to describe the impact of the rotavirus vaccine on hospitalizations among Haitian children younger than 5 years old during the first 5 years after introduction. This analysis includes all children with diarrhea who were enrolled as part of a sentinel surveillance system at two hospitals from May 2013 to April 2019. We compare the proportion of rotavirus-positive specimens in each post-vaccine introduction year to the pre-vaccine period. To account for the potential dilution of the proportion of rotavirus-positive specimens from a waning cholera outbreak, we also analyzed annual trends in the absolute number of positive stools, fit a two-component finite-mixture model to the negative specimens, and fit a negative binomial time series model to the pre-vaccine rotavirus-positive specimens to predict the number of rotavirus diarrhea hospital admissions in the absence of rotavirus vaccination. The overall percentage of rotavirus-positive specimens declined by 22% the first year after introduction, increased by 17% the second year, and declined by 33% to 50% the subsequent 3 years. All sensitivity analyses confirmed an overall decline. We observed a clear annual rotavirus seasonality before and after vaccine introduction, with the greatest activity in December through April, and a biennial pattern, with high sharp peaks and flatter longer periods of increased rotavirus activity in alternating years, consistent with suboptimal vaccination coverage. Overall, our study shows evidence that the introduction of the rotavirus vaccine reduced the burden of severe rotavirus diarrhea.

Caracterización clínico epidemiológica de la gastroenteritis por rotavirus. Estudio piloto. Hospital Pediátrico de Centro Habana. Noviembre 2017- abril 2018 / Clinical epidemiological characterization of rotavirus gastroenteritis. Pilot study. Paediatric Hospital of Centro Habana

La gastroenteritis causada por rotavirus constituye un importante problema de salud mundial, por lo que se recomienda incluir la vacunación contra el rotavirus en los programas de inmunización. Para evaluar el impacto de una futura introducción en Cuba de una vacuna contra este patógeno, resulta necesario crear una línea de base pre-vacunación de la carga de la gastroenteritis causada por este virus. Entre noviembre 2017 a abril 2018 se implementó en el Hospital Pediátrico de Centro Habana un sistema de vigilancia para la gastroenteritis causada por rotavirus. Se establecieron las definiciones para las categorías de caso sospechoso, probable y confirmado. Por cada niño captado se recogió una muestra de heces que se analizó con tiras rápidas y se confirmó la presencia de rotavirus por ELISA. Para determinar la severidad de la enfermedad se utilizó la escala de Vesikari. Los resultados fueron expresados en cifras absolutas y relativas, el análisis se realizó a través de la prueba de chi-cuadrado. Del total de ingresos por enfermedad diarreica aguda, el 26 por ciento cumplió los criterios de inclusión y el 46 por ciento resultó confirmado como rotavirus. El hacinamiento en el hogar y asistir al círculo infantil se comportaron como factores de riesgo. El servicio de gastroenterología absorbió la mayor carga de ingresos hospitalarios por esta causa. Los resultados mostrados validan la funcionalidad del sistema de vigilancia implementado y brindan nuevas evidencias sobre la carga de la enfermedad y la utilización de los servicios de un hospital pediátrico cubano, debido a la gastroenteritis provocada por rotavirus, lo que justifica la introducción de la vacuna(AU)

Gastroenteritis caused by rotavirus is a major global health problem, therefore it is recommended that vaccination against rotavirus be included in immunization programs. To evaluate the impact of a future introduction in Cuba of a vaccine against this pathogen, it is necessary to have a pre-vaccination baseline of the burden of gastroenteritis caused by rotavirus. Between November 2017 and April 2018, a surveillance system for gastroenteritis caused by rotavirus was implemented in the Paediatric Hospital of Centro Habana. Definitions were established for the categories of suspected, probable and confirmed cases. For each captured child, stool samples were collected, analyzed with rapid strips and confirmated by ELISA. To determine the severity of the disease, the Vesikari score was used. The results were expressed in absolute and relative figures; the analysis was performed through chi-square. Of the total admissions for acute diarrheal disease, 26 percent met the inclusion criteria and 46 percent were confirmed for rotavirus. Overcrowding at home and attending a day care center were risk factors. The gastroenterology service absorbed the greatest burden of hospital admissions for this cause. The results shown validate the role of the implemented surveillance system and provide new evidence on the burden of disease and use of services for rotavirus gastroenteritis in a cuban pediatric hospital(AU)

15-year experience with rotavirus vaccination in Mexico: a systematic literature review.

A systematic review was conducted in Mexico to consolidate and evaluate evidence after 15 years of rotavirus vaccination, according to the National Immunization Program. Five databases were screened to identify published articles (January 2000-February 2020) with evidence on all clinical and epidemiological endpoints (e.g. immunogenicity, safety, efficacy, impact/effectiveness) of rotavirus vaccination in Mexico. Twenty-two articles were identified (observational studies including health-economic models: 17; randomized controlled trials: 5). Fourteen studies evaluated a human attenuated vaccine (HRV), four studies evaluated both vaccines, and only two evaluated a bovine-human reassortant vaccine, with local efficacy data only for HRV. Local evidence shows vaccines are safe, immunogenic, efficacious, and provide an acceptable risk-benefit profile. The benefits of both vaccines in alleviating the burden of all-cause diarrhea mortality and morbidity are documented in several local post-licensure studies. Findings signify overall benefits of rotavirus vaccination and support the continued use of rotavirus vaccine in Mexico.

Effectiveness of monovalent rotavirus vaccine against hospitalizations due to all rotavirus and equine-like G3P[8] genotypes in Haiti 2014-2019.

BACKGROUND: Rotavirus vaccines are effective in preventing severe rotavirus. Haiti introduced 2-dose monovalent (G1P[8]) rotavirus vaccine recommended for infants at 6 and 10 weeks of age in 2014. We calculated the effectiveness of rotavirus vaccine against hospitalization for acute gastroenteritis in Haiti. METHODS: We enrolled children 6-59 months old admitted May 2014-September 2019 for acute watery diarrhea at any sentinel surveillance hospital. Stool was tested for rotavirus using enzyme immunoassay (EIA) and genotyped with multiplex one-step RT-PCR assay and Sanger sequencing for stratification by genotype. We used a case-negative design where cases were children positive for rotavirus and controls were negative for rotavirus. Only children eligible for vaccination were included and a child was considered vaccinated if vaccine was given ≥ 14 days before enrollment. We used unconditional logistic regression to calculate odds ratios and calculated 2-dose and 1-dose vaccine effectiveness (VE) as (1 - odds ratio) * 100. RESULTS: We included 129 (19%) positive cases and 543 (81%) negative controls. Among cases, 77 (60%) were positive for equine-like G3P[8]. Two doses of rotavirus vaccine were 66% (95% CI: 44, 80) effective against hospitalizations due to any strain of rotavirus and 64% (95% CI: 33, 81) effective against hospitalizations due to the equine-like G3P[8] genotype. CONCLUSIONS: These findings are comparable to other countries in the Americas region. To the best of our knowledge, this is the first VE estimate both against the equine-like G3P[8] genotype and from a Caribbean country. Overall, these results support rotavirus vaccine use and demonstrate the importance of complete vaccination.

Persistent infection with a rotavirus vaccine strain in a child suffering from Severe Combined Immunodeficiency in Argentina.

Due to the high burden of disease associated with rotavirus, the massive vaccination in children before six months of age has been encouraged. Currently licensed oral live vaccines have shown low risk of associated adverse events in the general population. Noteworthy, postmarketing reports of severe gastroenteritis with persistent vaccine viral shedding in children with severe combined immunodeficiency (SCID) have led companies to include this inborn error of immunity as an additional contraindication. SCID is not usually screened in newborns from developing countries. Therefore, the administration of live attenuated vaccines represents the first contact of these patients with life-threatening pathogens. We describe a clinical case of an infant with SCID who suffered from persistent rotavirus symptomatic diarrhea after receiving the rotavirus oral vaccine and was found to be infected with the vaccine strain. This case attempts to contribute to the discussion of those diseases that need to be incorporated into a screening program since an early diagnosis permits clinicians to withhold live attenuated immunization.

Rotavirus vaccination and stunting: Secondary Data Analysis from the Peruvian Demographic and Health Survey.

Rotavirus infection is the leading cause of acute diarrhea in children and is preventable with a vaccine. Malnutrition increases the risk for the development of enteric and respiratory diseases, but also diarrhea increases the risk for stunting, having a negative effect in height-for-age Z score (HAZ). Therefore, Rotavirus can be considered as one of the contributing factors to stunting. The objective was to determine if vaccination against rotavirus was associated with changes in HAZ of children aged 6-60 months. We analyzed the data of Demographic and Health Survey (DHS) 2015-2017 for Peru, which is a nationwide representative. We fitted linear regression models controlling for complex sampling. The vaccine coverage was close to 75.5%, and the mean HAZ was -0.76 standard deviations. After adjusting by demographic, health, and household characteristics, children who received rotavirus vaccine, had a mean HAZ 0.06 standard deviations higher than children who did not receive it. Additionally, BCG vaccination, a higher education level of the mother, a higher wealth index, and treating water for drinking were positively associated with HAZ. On the other hand, we found low birth weight, lack of flush toilet, and altitude higher than 2500 m above sea level negatively associated with HAZ. Rotavirus vaccine is associated with better anthropometric measurements.

Effect of the administration of Lactobacillus spp. strains on neonatal diarrhoea, immune parameters and pathogen abundance in pre-weaned calves.

Neonatal calf diarrhoea is one of the challenges faced by intensive farming, and probiotics are considered a promising approach to improve calves' health. The objective of this study was to evaluate the effect of potential probiotic lactobacilli on new-born dairy calves' growth, diarrhoea incidence, faecal score, cytokine expression in blood cells, immunoglobulin A (IgA) levels in plasma and faeces, and pathogen abundance in faeces. Two in vivo assays were conducted at the same farm in two annual calving seasons. Treated calves received one daily dose of the selected lactobacilli (Lactobacillus reuteri TP1.3B or Lactobacillus johnsonii TP1.6) for 10 consecutive days. A faecal score was recorded daily, average daily gain (ADG) was calculated, and blood and faeces samples were collected. Pathogen abundance was analysed by absolute qPCR in faeces using primers directed at Salmonella enterica, rotavirus, coronavirus, Cryptosporidium parvum and three Escherichia coli virulence genes (eae, clpG and Stx1). The faecal score was positively affected by the administration of both lactobacilli strains, and diarrhoea incidence was significantly lower in treated calves. No differences were found regarding ADG, cytokine expression, IgA levels and pathogen abundance. Our findings showed that oral administration of these strains could improve gastrointestinal health, but results could vary depending on the calving season, which may be related to pathogen seasonality and other environmental effects.

Effect of childhood rotavirus vaccination on community rotavirus prevalence in rural Ecuador, 2008-13.

BACKGROUND: Although live attenuated monovalent human rotavirus vaccine (Rotarix) efficacy has been characterized through randomized studies, its effectiveness, especially in non-clinical settings, is less clear. In this study, we estimate the impact of childhood Rotarix® vaccination on community rotavirus prevalence. METHODS: We analyse 10 years of serial population-based diarrhoea case-control study, which also included testing for rotavirus infection (n = 3430), and 29 months of all-cause diarrhoea active surveillance from a child cohort (n = 376) from rural Ecuador during a period in which Rotarix vaccination was introduced. We use weighted logistic regression from the case-control data to assess changes in community rotavirus prevalence (both symptomatic and asymptomatic) and all-cause diarrhoea after the vaccine was introduced. We also assess changes in all-cause diarrhoea rates in the child cohort (born 2008-13) using Cox regression, comparing time to first all-cause diarrhoea case by vaccine status. RESULTS: Overall, vaccine introduction among age-eligible children was associated with a 82.9% reduction [95% confidence interval (CI): 49.4%, 94.2%] in prevalence of rotavirus in participants without diarrhoea symptoms and a 46.0% reduction (95% CI: 6.2%, 68.9%) in prevalence of rotavirus infection among participants experiencing diarrhoea. Whereas all age groups benefited, this reduction was strongest among the youngest age groups. For young children, prevalence of symptomatic diarrhoea also decreased in the post-vaccine period in both the case-control study (reduction in prevalence for children <1 year of age = 69.3%, 95% CI: 8.7%, 89.7%) and the cohort study (reduction in hazard for receipt of two Rotarix doses among children aged 0.5-2 years = 57.1%, 95% CI: 16.6, 77.9%). CONCLUSIONS: Rotarix vaccination may suppress transmission, including asymptomatic transmission, in low- and middle-income settings. It was highly effective among children in a rural community setting and provides population-level benefits through indirect protection among adults.